Opioids Agonists (Exam II)

Question 1

What are opioids effects on the CO₂ medullary center?

Answer 1

• Opioids inhibit the CO₂ medullary center.

Question 2

Differentiate opioids from narcotics.

Answer 2

• Opioids = all exogenous substances that bind to endogenous opioid receptors.
• Narcotic = any substance that can produce dependence (stupor)

Question 3

What two types of opioid chemical structures are there?

Answer 3

• Phenanthrenes
• Benzylisoquinolines

Question 4

What types of drugs are Phenanthrenes?
What types of drugs are benzylisoquinolines?

Answer 4

• Phenanthrenes: Morphine & codeine
• Benzylisoquinoline: Papaverine

Question 5

What is papaverine mostly used for?

Answer 5

Treating intra-arterial barbiturate administration (dilates the highly constricted artery).

Question 6

What portions of the brain are the source of descending inhibitory signals?

Answer 6

• Thalamus
• PAG
• Locus Coeruleus

Question 7

What endogenous substances have the same effect as opioids?

Answer 7

Endorphins, Enkephalins, and Dynorphines.

Question 8

Presynaptic inhibition of what neurotransmitters occurs with opioid administration?

Answer 8

• ACh
• Dopamine
• NE
• Substance P

Question 9

How do opioids modulate pain at the cellular level?

Answer 9

At pre/postsynaptic opioid receptor sites in CNS
- ↑ K⁺ permeability (hyperpolarization)
- inactivate Ca⁺⁺ channel

Question 10

Where are opioid receptors located in the brain?

Answer 10

• PAG
• Locus Coeruleus
• RVM (rostral ventral medulla)
• Hypothalamus

Question 11

Where is the primary site of opioid receptors in the spinal cord?

Answer 11

Substantia gelatinosa (aka Laminae 2)

Question 12

Where is/are opioid receptors found outside the CNS?

Answer 12

• Sensory neurons & immune cells

Question 13

What are the four (most important) types of opioid receptors?

Answer 13

• Μu₁ (μ₁)
• Μu₂ (μ₂)
• Κappa (κ)
• Delta (δ)

Question 14

Which opioid receptor(s) is/are responsible for respiratory depression & physical dependence?

Answer 14

• Μu₂ and δ

Question 15

Which receptors are responsible for constipation?

Answer 15

• Μu₂ primarily
• δ (less)

Question 16

Which receptors can cause urinary retention?
Are there any receptors that cause diuresis when bound?

Answer 16

• Retention: Μu₁ and δ
• Diuresis: κ

Question 17

All opioid receptors induce analgesia at both the brain and the spinal cord. T/F?

Answer 17

• False. Μu₂ receptors only cause analgesia at the spinal cord level.

Question 18

What opioid receptors have low abuse potential when bound?

Answer 18

Μu₁ and κ

Question 19

Which opioid receptor is responsible for euphoria, bradycardia, hypothermia, and miosis when bound?

Answer 19

Mu1

Question 20

What agonists bind to each of the four opioid receptors?

Answer 20

• Mu1 & Mu2 = endorphins, morphine, synthetics.
• κ = dynorphins.
• δ = enkephalins.

Question 21

Describe the adverse side effects of opioids on the cardiovascular system.

Answer 21

• ↓BP from ↓SNS tone
• ↓HR or histamine release = ↓BP

Question 22

What possible cardiovascular benefits do opioids provide?

Answer 22

• Myocardial ischemia protection (decrease oxygen demand)

Question 23

What are the respiratory effects of opioids?
What would symptoms of overdose be?

Answer 23

• Depressed CNS response to CO₂ causing a right shift of PaCO₂ (↑)
• Overdose = apnea, miosis, coma.

Question 24

What drug would treat opioid ventilatory depression but not reverse analgesia?
How?

Answer 24

• Physostigmine would by increasing CNS ACh levels.

Question 25

What would cause a leftward shift in PaO₂?
What would cause a rightward shift?

Answer 25

• Leftward: Metabolic acidosis (to breathe off all that CO₂)
• Rightward: sleep → opiates → anesthesia

Question 26

Why should caution be used when administering opioids to head trauma patients?

Answer 26

• Opioids ↓CBF and possibly ICP

Question 27

What musculoskeletal abnormality occurs with opioid administration?
What makes this condition worse?
How is it treated?

Answer 27

• Skeletal chest wall and abdominal muscle rigidity.
• Mechanical ventilation
• Muscle relaxants and/or naloxone

Question 28

What are sphincter of Oddi spasms?
Which drugs can cause this?

Answer 28

• Biliary smooth muscle spasm
• Fentanyl (99%), Morphine (53%), and Meperidine (61%). (Opioids)

Question 29

What drugs should be used for ERCP cases?

Answer 29

• Non-opioids (multimodal approach w/ NSAIDs, gabapentin, etc.)

Question 30

How are opioid-induced sphincter of Oddi spasm’s treated?

Answer 30

• Naloxone
• Glucagon (2mg IV given incrementally) and causes no opioid antagonism.

Question 31

How long does it take (generally) to develop tolerance to opioids?
What causes tolerance?

Answer 31

• 2-3 weeks
• Downregulation (desensitized and decreased number of opioid receptor)

Question 32

What is the dosage of morphine?
When does it peak?
How long does it last?

Answer 32

• 1 - 10 mg IV
• Peak: 15 - 30 minutes
• Duration: 4-5 hours

Question 33

How is morphine metabolized?
What is the active metabolite and its significance?

Answer 33

• Glucuronidation in the liver.
• Morphine-6-glucuronide = comprises only 5-25% of morphine metabolites but is an active anaglesic causing late resp depression.

Question 34

What would occur with morphine overdose in a renal failure patient?

Answer 34

• Prolonged ventilatory depression.

Question 35

What receptors does meperidine agonize?

Answer 35

• μ and κ receptors
• α2 receptors as well

Question 36

What are the analogues of meperidine?
What other drugs does meperidine have a similar organic structure to?

Answer 36

• Fentanyl & it’s derivatives
• Lidocaine & Atropine

Question 37

How potent is Meperidine? (comp)
How long does it last?

Answer 37

• 10% as potent as morphine
• Duration: 2-4 hours

Question 38

What is the primary indication for meperidine?
What dose is used?

Answer 38

• Post-operative shivering
• 12.5mg IV

Question 39

When should meperidine not be used?

Answer 39

• Bronchoscopies (promotes coughing)

Question 40

How potent is fentanyl?

Answer 40

• 75 - 125 x morphine.